Genomic Vision offers a novel multigene approach for the clinical research of


Hereditary Colorectal Cancer

Lynch syndrome refers to the major hereditary colorectal cancer

Colorectal cancer is the second most common cancer in women and the third among men. Lynch syndrome (LS) is a hereditary non-polyposis colorectal cancer (HNPCC), the most common colorectal cancer linked to a genetic predisposition; it is estimated to account for up to 5% of all colorectal cancers. The patients with Lynch syndrome also have an increased risk of cancers of the endometrium, ovary, stomach, small intestine, gallbladder ducts and upper urinary tract. Colorectal cancer is, in many cases, a treatable disease if caught early.

A cancer predominantly caused by a mutation in one of the DNA mismatch repair genes

Mutations inside MLH1, MSH2, MSH6 and PMS2, the genes involved in the DNA mismatch repair (MMR), boost the risk of developing LS. Mutations in any of these genes impair the suitable repair of DNA replication errors that accumulate in cells, promoting their aberrant proliferation and leading to cancer. MLH1 and MSH2 germline mutations account for approximately 90% of mutations in families with LS. Besides the point mutations, large genomic rearrangements in the MMR genes can be the cause of inherited colorectal cancer. These large scale genomic aberrations are present in approximately 20% of patients.

 As the diagnostic of HNPCC is challenging, many patients with Lynch Syndrome remain undiagnosed

In cancers linked to the Lynch Syndrome, the MMR system is defective and leads to microsatellite instabilities. Immunohistochemistry (IHC) methods help clinicians identify the MMR gene that most likely harbors a germline mutation. Following a positive IHC diagnosis, patients are oriented towards genetic testing. A significant fraction of LS individuals with large genomic deletions or duplications in the MMR genes can be challenging to detect by means of traditional methods. PMS2 genomic aberrations are complicated by the occurrence of sequence exchange events between the duplicated regions of PMS2 and its pseudogene PMS2CL. As a consequence of this gene conversion, some of mutations are missed or incorrectly located via the routine methods.

Genomic Vision brings a new approach to complement conventional methods

in the understanding of the hereditary colorectal cancer